Komiskey: Lithium/Metals

Question 1

Can metals be broken down to reduce toxicity?

Answer 1

No

Question 2

What is lithium mainly used to treat?

Answer 2

Manic episodes of bipolar disorder

Non-FDA approved uses:

• prophylaxis of cluster HA’s
• hyperthyroidism
• adjuvant therapy in resistant depression (unipolar state)

Question 3

How is lithium metabolized?

Answer 3

It does not undergo metabolism - elimination is RENAL

Question 4

How much lithium is reabsorbed and where?

Answer 4

70%; proximal convoluted tubule

Question 5

What Increases Li levels?

Answer 5

DANC! because you're high on Li:
Diuretics (thiazides & loops)
ACE-inhibitors and ARBS
NSAIDS (cox-2 inhibitors, indomethacin)
Clonazepam

Question 6

What Decreases Li levels? (increase Li urinary excretion)

Answer 6

AX it away with carbs
Acetazolamide; xanthine preparations
Sodium Bicarb

Question 7

What is Li’s affect on ADH?

Answer 7

Li decreases amount of AQP2 channels –> ADH can’t work efficiently –> drink a lot/pee a lot

Question 8

What is unique about Li toxicity?

Answer 8

It precipitates its own toxicity: polyuria & resistance to ADH = volume depletion and increased renal REabsorption of Li

Question 9

How much lead in the blood gets filtered through the kidneys?

Answer 9

65%

Question 10

Pb (lead) redistributes to the ___________ and acts like ______.

Answer 10

bone; Ca2+

Question 11

Toxicity of Pb

Answer 11

• neurotoxic, nephrotoxic, immunotoxic
• alters heme synthesis, bone/teeth metabolism
• probable carcinogen
• increases BP/HTN

Question 12

Pb causes a ____________ in GFR

Answer 12

decrease

Question 13

Which causes more kidney problems - organic or inorganic Pb?

Answer 13

inorganic

Question 14

What are the three forms of mercury and where do they mainly have effects?

Answer 14

elemental (liquid at room temp)

inorganic: GI effects (10% GI absorption)
organic: mental effects (90% GI absorption)

Question 15

Common sources of mercury exposure?

Answer 15

Occupational - miners, dental offices

Seafood (bigger fish - bad)

Question 16

What is the toxicity MOA of mercury?

Answer 16

Most likely binds sulfhydryl

Question 17

What are mercury’s target organs?

Answer 17

Kidney and CNS

Question 18

Symptoms of mercury poisoning?

Answer 18

Erethism (irritability, memory loss), mercurialentis (brown band in eye from Hg deposit), cancer, cerebral palsy in fetus

Question 19

Source of Organic Methyl Hg?

Answer 19

Fish

Question 20

Sources of organic Ethyl Hg?

Answer 20

Thimerosal (in vaccinations)

Question 21

Can mercury exposure/thimerosal cause autism?

Answer 21

No - Studies show a stronger correlation with ADD

Question 22

Sources of Cadmium?

Answer 22

Cigarette smoke
copper, lead, zinc from car exhaust
natural rock weathering

used in fertilizer - FOOD is most common route of exposure

Question 23

How is Cd distributed in the body?

Answer 23

binds to albumin in plasma & RBCs

gets sent to liver, pancreas, prostate, kidneys (50-75% is in liver & kidneys)

Question 24

How is Cd trapped in the kidney and what is its half-life?

Answer 24

Metallothionein (it’s synthesis is induced by Cd)

Cd 1/2 life = 20-30 years

Question 25

**What is the mechanism of Cd toxicity in the kidney?

Answer 25

(bold on ppt): - Free Cd binds to kidney glomerulus - causes proximal tubule dysfunction

Question 26

**What is the effect of Cd on the body's organs?

Answer 26

TWO MAIN ORGANS EFFECTED: bones and kidneys. kidney damage is irreversible. Kidneys:leads to increased proteinuria; also: gout, hyperuricemia, hyperchloremia; kidneys can shrink up to 30% - reduction in GFR, increase in beta2-microglobulin Other organs: lung damage, osteomalacia (itai-itai), high BP

Question 27

What staple food contains arsenic?

Answer 27

Rice. Recommendation: cook it in 5-6x rice volume in water. brown rice has more As than white.

Question 28

How is As distributed in the body?

Answer 28

Mimics phosphate detoxified by methylation (decreased rates lead to increased toxicity) can cross placenta accumulates in LIVER, KIDNEY, heart and lungs half-life: 10 hours; excretion via kidneys

Question 29

How to treat metal poisoning?

Answer 29

Chelaters: bind directly with metal ions to form stable complexes that remove the metal from competition within body's cells Chelated metals are water soluble -> excreted by kidney

Question 30

What are the most stable chelates?

Answer 30

Those with 5 or 6 membered ring

Question 31

What are characteristics of ideal chelating agents?

Answer 31

water soluble, resistant to biotransformation, capable of forming non-toxic complexes with toxic metals, be excreted from the body, have a LOW affinity for essential metals

Question 32

Common chelating agents?

Answer 32

- Dimercaprol (aka BAL: British Anti-Lewisite) (must be given parenterally) - Dimercaptosuccinic acid (DMSA) (USA's oral version of BAL) - Dimercaptopropanesulfonate (DMPS) (EU's oral) - D-penicillamine (copper) - Deferoxamine (iron) - Ethylenediamintetraacetic acid (ETDA) - Calcium Disodium Edetate (CaNa2) (lead)

Question 33

What can dimercaprol (BAL) treat?

Answer 33

``` HAPA: Hg As Pb Au ```

Question 34

What is the dimercaprol/BAL dosage?

Answer 34

needs to form a 2:1 complex

Question 35

Side effects of dimercaprol/BAL?

Answer 35

highlighted: Nephrotoxicity

Question 36

What is used to treat lead toxicity?

Answer 36

CaNa2EDTA

Question 37

What is DMSA used to treat?

Answer 37

``` HAPC: Hg As Pb Cu ---> as opposed to dimercaprol, DMSA can treat copper toxicity ``` Also: Sb (antimony), Bi (bismuth)

Question 38

Where is DMSA active?

Answer 38

extracellular space

Question 39

When will nephrotoxicity appear after treatment with D-penicillamine for copper?

Answer 39

4-18 months